Role of G-protein-coupled signaling in the induction and regulation of dendritic cell function by Toxoplasma gondii.

The induction of IL-12 from dendritic cells (DCs) is thought to be a critical step in the initiation of IFN-gamma-dependent cell-mediated immunity to many intracellular pathogens. We have studied this response using an in vivo model in which IL-12 production by splenic CD8alpha+ DCs is followed after systemic injection of a soluble extract (STAg) of the protozoan parasite Toxoplasma gondii. Our findings indicate that G-protein-coupled signaling through the chemokine receptor CCR5 plays a major role in the induction of IL-12 from these cells and that downregulation of CCR5 function through endogenously produced lipoxin explains the loss of responsiveness (paralysis) seen upon STAg reinjection. Recent data on the inductive and regulatory pathways involved and their role in governing host resistance to parasite infection in vivo will be discussed.